Risperidone reduction of amphetamine-induced self-injurious behavior in mice

Wagner, George C.; Avena, Nicole M.; Kita, Taizo; Nakashima, Toshikatsu; Fisher, Hans; Halladay, Alycia

doi:10.1016/j.neuropharm.2003.11.009

Cited by 20 publications

(15 citation statements)

References 41 publications

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“…All of the mice showed at least one of the following behaviors: stereotypic sniffing, vigorous chewing, increased locomotor activity, head-bobbing, and excessive salivation, as previously described (Eisch et al, 1998;Wagner et al, 2004). These observations were subjective and qualitative, but not quantitative, as the purpose of the observation was to confirm the proper METH injection.…”

Section: Behavior and Self-injury After Meth Administrationsupporting

confidence: 59%

“…In the most severe case, an FosB(À/À) mouse had 0.5 Â 1 cm detachment of skin from its chest and the ventral part of the neck, and the underlying musculature was exposed. For the remaining three bleeding mice, we were unable to identify any obvious skin lesion, though smaller injuries to the tongue or oral cavity due to oral dyskinesia could have possibly occurred (Wagner et al, 2004). A Fisher's exact probability test showed that FosB(À/À) mice were significantly more prone to bleeding (p ¼ 0.023) and self-injury (p ¼ 0.049) compared to their ( + / + ) littermates after a single 10 mg/kg METH injection, suggesting that FosB deficiency increases the incidence of METH-induced self-injuries.…”

Section: Enhanced Meth Neurotoxicity In Fosb(à/à) Micementioning

confidence: 93%

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FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

Kuroda

Ornthanalai

Kato

et al. 2009

Neuropsychopharmacol

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Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (À/À) mice. After a 10 mg/kg methamphetamine injection, FosB(À/À) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(À/À) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(À/À) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(À/À) mice. In addition, methamphetamine-treated FosB(À/À) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood-brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood-brain barrier, and metabolism of serine and glycine, which are important glial modulators of nerve cells.

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Section: Behavior and Self-injury After Meth Administrationsupporting

confidence: 59%

Section: Enhanced Meth Neurotoxicity In Fosb(à/à) Micementioning

confidence: 93%

FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

Kuroda

Ornthanalai

Kato

et al. 2009

Neuropsychopharmacol

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“…40 The SIB is most profound feature of Lesch-Nyhan syndrome and common complication in autism, mental retardation and other neuropsychiatric disorders. 19 Considerable amount of evidence points to dysfunction in central dopaminergic neurons and permissive role of serotonergic system. 21 In addition, experimental studies show that an early depletion of dopamine is a necessary condition for SIB induced by dopamine receptor agonists in the adulthood.…”

Section: Discussionmentioning

confidence: 99%

“…These self-directed actions fulfilled the criteria for selfinjurious behavior (SIB), as previously defined by others. 19,20 The SIB is a hallmark of the Lesch-Nyhan syndrome and its neurological basis is still poorly understood. Clinical and experimental data suggest that neonatal loss of central dopaminergic transmission, increased serotonergic activity and deficient neurotrophic factors play important roles.…”

Section: Introductionmentioning

confidence: 99%

Proclivity to self-injurious behavior in MRL-lpr mice: implications for autoimmunity-induced damage in the dopaminergic system

et al. 2007

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Systemic lupus erythematosus is frequently accompanied by psychiatric manifestations of unknown origin. Although damage of central neurons had been documented, little is known about neurotransmitter systems affected by the autoimmune/inflammatory process. Recent studies on lupus-prone MRL-lpr mice point to imbalanced dopamine function and neurodegeneration in dopamine-rich brain regions. We follow up on anecdotal observations of singly housed mice developing chest wounds. Compulsive grooming and/or skin biting accounted for open lesions, lending itself to the operational term 'self-injurious behavior' (SIB). Low incidence of spontaneous SIB increased significantly after repeated injections of dopamine-2/ 3 receptor (D2/D3R) agonist quinpirole (QNP). To further probe the dopaminergic circuitry and examine whether SIB is associated with development of lupus-like disease, we compared behavioral responses among cohorts that differed in the immune status. Two-week treatment with QNP (intraperitoneal, 0.5 mg kg À1 body weight per day) induced SIB in 60% of diseased MRL-lpr mice, and exacerbated their splenomegaly. Although increased grooming and stereotypy were observed in less symptomatic MRL þ / þ controls, only one mouse (10%) developed SIB. Similarly, SIB was not seen in young, asymptomatic groups despite dissimilar ambulatory responses to QNP. In situ hybridization revealed treatment-independent upregulation of D2R mRNA in substantia nigra of diseased MRL-lpr mice. The above results suggest that development of systemic autoimmunity alters sensitivity of the dopaminergic system and renders MRL-lpr mice prone to SIB. Although pathogenic factors were not examined, we hypothesize that immune and endocrine mechanisms jointly contribute to early neuronal damage, which underlies behavioral deficiency in the adulthood.

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“…Observed stereotypies included self-injurious skin-picking and chestbiting behavior that became rather severe in four out of six mice, resulting in tissue injury and bleeding. It should be noted that drug-induced self-injurious behavior in the mouse has previously been reported following high or repeated doses of a range of classical drugs, including caffeine (Mardikar et al, 1969), clonidine (Razzak et al, 1975), L-type calcium channel agonists ( þ / À ) Bay K 8644 and FPL 64176 (Jinnah et al, 1999;Kasim et al, 2002), METH (Shishido et al, 2000;Kita et al, 2000), amphetamine (Wagner et al, 2004), and pemoline (Devine 2012). Nevertheless, no MDPV-induced self-injurious behavior was observed when the drug was administered at the cool 20-1C ambient temperature, perhaps suggesting a potential role of ambient temperature in MDPV-induced selfinjurious behavior.…”

Section: 4-methylenedioxypyrovalerone In Micementioning

confidence: 99%

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Fantegrossi

Gannon

Zimmerman

et al. 2012

Neuropsychopharmacol

138

151

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In recent years, synthetic analogues of naturally occurring cathinone have emerged as psychostimulant-like drugs of abuse in commercial 'bath salt' preparations. 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of these illicit products, and its structural similarities to the more well-known drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) suggest that it may have similar in vivo effects to these substances. In these studies, adult male NIH Swiss mice were trained to discriminate 0.3 mg/kg MDPV from saline, and the interoceptive effects of a range of substitution doses of MDPV, MDMA, and METH were then assessed. In separate groups of mice, surgically implanted radiotelemetry probes simultaneously monitored thermoregulatory and locomotor responses to various doses of MDPV and MDMA, as a function of ambient temperature. We found that mice reliably discriminated the MDPV training dose from saline and that cumulative doses of MDPV, MDMA, and METH fully substituted for the MDPV training stimulus. All three drugs had similar ED 50 values in this procedure. Stimulation of motor activity was observed following administration of a wide range of MDPV doses (1-30 mg/kg), and the warm ambient temperature potentiated motor activity and elicited profound stereotypy and self-injurious behavior at 30 mg/kg. In contrast, MDPV-induced hyperthermic effects were observed in only the warm ambient environment. This pattern of effects is in sharp contrast to MDMA, where ambient temperature interacts with thermoregulation, but not locomotor activity. These studies suggest that although the interoceptive effects of MDPV are similar to those of MDMA and METH, direct effects on thermoregulatory processes and locomotor activity are likely mediated by different mechanisms than those of MDMA.

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Risperidone reduction of amphetamine-induced self-injurious behavior in mice

Cited by 20 publications

References 41 publications

FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

Proclivity to self-injurious behavior in MRL-lpr mice: implications for autoimmunity-induced damage in the dopaminergic system

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

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